An IKKα-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence

Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate I kappa B kinase a (IKK alpha) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKK alpha are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKK alpha phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKK alpha-BMI1 pathway is also activated in human PCa.